<scp>SMARCA4</scp> ‐deficient rhabdoid tumours show intermediate molecular features between <scp>SMARCB1</scp> ‐deficient rhabdoid tumours and small cell carcinomas of the ovary, hypercalcaemic type
Mamy Andrianteranagna, Joanna Cyrta, Julien Masliah‐Planchon, Karolina Nemes, Alice Corsia, Amaury Leruste, Dörthe Holdhof, Uwe Kordes, Daniel Orbach, Nadège Corradini, Natacha Entz‐Werlé, Gaëlle Pierron, Marie‐Pierre Castex, A. Brouchet, Noëlle Weingertner, Dominique Ranchère, Paul Fréneaux, Olivier Delattre, Jonathan W. Bush, Alexandra Léary, Michael C. Frühwald, Ulrich Schüller, Nicolas Servant, Franck Bourdeaut
Abstract
Abstract Extracranial rhabdoid tumours (ECRTs) are an aggressive malignancy of infancy and early childhood. The vast majority of cases demonstrate inactivation of SMARCB1 (ECRT SMARCB1 ) on a background of a remarkably stable genome, a low mutational burden, and no other recurrent mutations. Rarely, ECRTs can harbour the alternative inactivation of SMARCA4 (ECRT SMARCA4 ) instead of SMARCB1. However, very few ECRT SMARCA4 cases have been published to date, and a systematic characterization of ECRT SMARCA4 is missing from the literature. In this study, we report the clinical, pathological, and genomic features of additional cases of ECRT SMARCA4 and show that they are comparable to those of ECRT SMARCB1. We also assess whether ECRT SMARCB1 , ECRT SMARCA4 , and small cell carcinomas of the ovary, hypercalcaemic type (SCCOHT) represent distinct or overlapping entities at a molecular level. Using DNA methylation and transcriptomics‐based tumour classification approaches, we demonstrate that ECRT SMARCA4 display molecular features intermediate between SCCOHT and ECRT SMARCB1 ; however, ECRT SMARCA4 appear to be more closely related to SCCOHT by DNA methylation. Conversely, both transcriptomics and DNA methylation show a larger gap between SCCOHT and ECRT SMARCB1 , potentially supporting their continuous separate classification. Lastly, we show that ECRT SMARCA4 display concomitant lack of SMARCA4 (BRG1) and SMARCA2 (BRM) expression at the protein level, similar to what is seen in SCCOHT. Overall, these results expand our knowledge on this rare tumour type and explore the similarities and differences among entities from the ‘rhabdoid tumour’ spectrum. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.